KETONIL ® (solution for injection)

Clear liquid from colourless to light-yellow with a specific odour.

1 ml of the product contains active substance (mg):

- ketoprofen – 100,0.

Excipients: citric acid, benzyl alcohol, L-arginine, water for injection.

ATCvet classification code QM01 – anti-inflammatory and antirheumatic veterinary medicinal products. QM01AE03 – Ketoprofen.

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid derivative group. It has anti-inflammatory, analgesic and antipyretic effects. The mechanism of action of ketoprofen is based on inhibition of the cyclooxygenase (COX) enzyme and suppression of prostaglandin and thromboxane synthesis. At therapeutic doses, it predominantly inhibits cyclooxygenase-2 (COX-2), providing anti-inflammatory and antipyretic effects, and has little effect on cyclooxygenase-1 (COX-1), which results in a low incidence of adverse reactions such as bleeding, ulcer formation and impairment of renal function.

The analgesic effect of ketoprofen is associated with direct inhibition of bradykinin, which stimulates pain receptors (nociceptors) and thereby provokes pain. In addition to its anti-bradykinin activity, the drug exerts a central effect by reducing pain perception in the central nervous system.

In horses, ketoprofen neutralises the effect of endotoxins and counteracts intestinal spasms caused by bradykinin.

After intramuscular administration, ketoprofen is rapidly absorbed. More than 98% of the drug binds to plasma proteins and accumulates in inflamed tissues. In cattle, peak plasma levels of ketoprofen (8,025 ± 1.9 µg/ml) are reached in less than one hour after intramuscular administration. High concentrations of ketoprofen are found in synovial fluid, where its level is higher than in plasma, while the half-life is 2–3 times longer than in plasma.

After intramuscular administration to cattle, the maximum plasma concentration of ketoprofen is observed within 30–60 minutes, and in horses within 60 minutes. Bioavailability after intramuscular administration in cattle and pigs is 90–100%, and in horses 70%. The volume of distribution and clearance are approximately 0,17 l/kg and 0,3 l/kg, respectively.

After a single intramuscular administration to piglets, ketoprofen reaches a maximum plasma concentration of 16,6 mg/l at 0,67 h, with a half-life of 2,21 h. The area under the concentration–time curve AUC0–t is 54,3 mg•h/l.

The plasma half-life of ketoprofen after intramuscular administration is 2–3 hours. Approximately 95% of ketoprofen is bound to plasma proteins. Ketoprofen is metabolised in the liver to inactive metabolites (conjugates with glucuronic acid), which are excreted mainly in the urine and, to a lesser extent, with faeces. Small amounts of ketoprofen may be detected in the milk of treated animals.

Cattle: reduction of inflammation, pain and/or pyrexia associated with respiratory diseases or disorders of the musculoskeletal system (arthritis, arthrosis, laminitis, osteoarthritis, synovitis, tendinitis, dislocations, trauma and others), as well as in acute mastitis (as adjunct therapy) in combination with antimicrobial products.

Horses (sport horses): reduction of inflammation and pain in acute and chronic inflammatory conditions of the musculoskeletal system (laminitis, osteoarthritis, synovitis, tendinitis, etc.), reduction of postoperative pain and inflammation in colic.

Pigs: reduction of inflammation, pain and/or pyrexia associated with respiratory diseases or MMA syndrome (metritis-mastitis-agalactia), in combination with antimicrobial therapy.

The product is administered intramuscularly or intravenously at the following doses:

- cattle – intramuscularly or intravenously once daily at a dose of 3 ml of the product per 100 kg body weight (equivalent to 3 mg of ketoprofen per 1 kg body weight) for 1–3 days.

- horses (sport horses) – intravenously once daily at a dose of 1 ml of the product per 45 kg body weight (equivalent to 2,22 mg of ketoprofen per 1 kg body weight) for 3–5 days.

For treatment of colic in horses, a single administration is sufficient. If necessary, a repeated injection is possible only after additional examination of the animal.

- pigs – intramuscularly once daily at a dose of 0,3 ml of the product per 10 kg body weight (equivalent to 3 mg of ketoprofen per 1 kg body weight) for 1–3 days.

Do not use in animals with duodenal ulcer or haemorrhagic syndrome.

Do not use in animals with cardiac or hepatic diseases.

Do not use in animals with acute renal failure.

Do not use in animals with hypersensitivity to ketoprofen.

Do not use in foals less than 15 days of age.

Do not use in pregnant mares.

Do not use in food-producing horses whose meat is intended for human consumption.

Do not use concomitantly with non-steroidal anti-inflammatory drugs or glucocorticosteroids.

Gastric or intestinal irritation or ulceration and renal failure may occur, associated with the mechanism of action of ketoprofen. After intramuscular administration, a local swelling may occur at the injection site, painful on palpation, which disappears within one week after the end of treatment. Repeated administration in pigs may cause loss of appetite. Allergic reactions to the product are very rare. If allergic reactions occur, treatment must be discontinued.

Intra-arterial injection, overdose or prolonged treatment must be avoided. Use with caution in animals with dehydration, hypovolaemia and hypotension due to the risk of renal failure. Ketoprofen is not recommended for foals under one month of age.

When used in animals under 6 weeks of age, ponies or elderly animals, the dose must be determined with particular accuracy; such animals require very careful clinical monitoring. Animals must have free access to drinking water throughout the treatment period.

In horses with colic, repeated administration of the product is possible only after careful re-examination of the animal.

Do not use in pregnant mares. Pregnant sows may be treated only after a benefit/risk assessment performed by a veterinary surgeon. The product may be used in lactating cows without restriction.

Do not use concomitantly with other medicinal products of the propionic acid derivative group, diuretics or anticoagulants. Do not use concomitantly with other non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticosteroids.

Meat intended for human consumption may be used 4 days after the last administration of the product. Before this time, such products must be disposed of or used for feeding non-productive animals in accordance with the advice of a veterinary surgeon.

Milk may be used for human consumption without restriction.

Vials of neutral glass type NS-1, NS-2, USP-1, closed with rubber stoppers and sealed with aluminium caps, containing 10, 20, 50 or 100 ml. Secondary packaging: cardboard box.

Store in a dry, dark place out of the reach of children, at a temperature from 5 to 25 °C.

2 years.

Shelf life after first opening of the vial – 7 days.